Diagnosing pulmonary tuberculosis

The gold standard for tuberculosis diagnosis is being able to grow M. tuberculosis from a sputum sample. However, this takes weeks or months and requires specialised facilities that are not available in every setting. If possible, at least one good specimen should be sent for culturing and drug susceptibility testing, even though treatment of active disease cannot wait for culturing results.

Diagnosis and treatment is normally based upon a combination of other factors, including symptoms, chest X-rays and examination of sputum under the microscope. All of these can be influenced by HIV infection.

Chest X-rays in a person with classic pulmonary tuberculosis usually reveal cavities in the upper lobes of the lung. However in people with HIV, the X-ray might look normal or look similar to the effects of other lung diseases. Importantly, X-rays cannot distinguish between active and treated tuberculosis.

When a patient has classic pulmonary tuberculosis, sputum often contains M. tuberculosis bacteria. These can be seen under the microscope after staining with medical dyes. A diagnosis for pulmonary tuberculosis can be made on the basis of at least two positive results out of two or three smears. This test can be performed in most clinic laboratories and plays a pivotal role in most tuberculosis control programmes. However, this method is far less reliable in people with HIV. In some parts of the world, smears from over half the cases of active tuberculosis test negative.

One problem is that it can be very difficult to obtain a sputum sample from someone with HIV. Sometimes, in a person who does not have a productive cough, a doctor will try to induce a specimen by spraying saline solution into the back the throat.

Even if a sputum sample is obtained, it can be difficult to detect TB bacteria in the sample, leading to a smear-negative diagnosis despite the presence of symptoms that suggest TB.

If both the specimens are smear negative, but a chest X-ray (if available) suggests TB, a diagnosis of smear-negative TB can be made if the clinician decides to treat with a full course of TB treatment and monitor closely for the response. In addition, a diagnosis of smear-negative TB can be reached once a specimen sent for culture comes back positive for M. tb.

There are several ‘danger signs’ that indicate a need for emergency antibiotic treatment in the smear-negative patient, according to the World Health Organization's 2006 guidelines on smear-negative TB,¹ including if the person is unable to walk unaided, has a respiratory rate over 30 per minute, a fever higher than 39 °C or a pulse rate of over 120 per minute.

In cases where someone is dangerously ill but the diagnosis is unclear or cannot be reached rapidly enough, the new WHO recommendations suggest sending the person as quickly as possible to a higher-level facility. If that isn’t possible, then the person should be immediately put on a broad-spectrum parenteral antibiotic, and, depending upon the CD4 cell counts or clinical setting, treatment for Pneumocystis pneumonia (PCP, also known as Pneumocystis jirovecii pneumonia) should be considered as well.

Healthcare workers at all levels need to be on the lookout for extrapulmonary TB in people with HIV. In addition to a cough (which may or may not be present), a variety of symptoms, fevers with night sweats, weight loss, difficulty breathing, swollen lymph nodes, or swollen arms and legs, or a chronic headache or altered mental state could all be suggestive of TB in another part of the body.

Extrapulmonary TB can take such a wide variety of forms because in a person with advanced immunosuppression, the mycobacterium can infect tissues in almost any part of the body. The most common areas include the lymph nodes (especially in the neck or under the arms), the pleura (the membrane that lines the lungs and chest cavity — though usually just one side is infected) and disseminated tuberculosis (spread to a number of sites in the body). M.tuberculosis can also infect the tissue around the heart, or the meninges (the membranes covering the brain and spinal cord) and other areas.

But it is important to note that extrapulmonary TB is even more commonly associated with HIV status than smear negative pulmonary TB, so learning the patient’s HIV status is all the more essential for a diagnosis. According to WHO about one-third of deaths in HIV-positive Africans are due to disseminated tuberculosis but only about half of HIV-positive patients who die from disseminated tuberculosis are diagnosed before death.

The revised definition of extrapulmonary TB requires obtaining a positive result, by smear microscopy or culture, on at least one biological specimen from the site of infection. Or, a diagnosis may be made if there is histological or strong clinical evidence consistent with extrapulmonary TB in a person with (or strongly suspected of having) HIV, and a decision to treat with a full course of anti-TB treatment.

So far, attempts to develop a fast, simple and accurate blood test for tuberculosis have failed to produce an accurate and reliable test.² However, a number of new techniques are being explored that may help diagnose both latent and active disease in patients coinfected with tuberculosis and HIV.³